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Introduction The clinical presentation of lower gastrointestinal bleeding (LGIB) is variable in severity, cause and potential investigations. The British Society of Gastroenterology recently published LGIB guidelines, recommending CT angiography (CT-A) for haemodynamically unstable patients, defined by shock index (SI) greater than 1. The aim of this study was to assess the use and role of CT-A in diagnosing LGIB, by assessing the pickup rate of active LGIB defined by contrast extravasation or ‘blush’ and to determine any association between positive CT-A with various patient and clinical characteristics. Methods A retrospective analysis was carried out of 4 years of LGIB admissions. Demographics, inpatient observations and use of blood products were acquired. Vital signs nearest the time of CT-A plus abnormal vital signs preceding imaging were used to calculate SI, Age SI, National Early Warning Score 2 (NEWS2) and Standardised Early Warning Score (SEWS). A consultant gastrointestinal radiologist further reviewed all consultant-reported scans. Results In total, 930 patients were admitted with LGIB. Median age was 71 years and 51% were male; 179 (19.2%) patients received red blood cell transfusion and 93 patients (10%) underwent CT-A, who were older and were likely to be hypotensive and receive red cell transfusions. Following exclusions, 92 CT-As were included in the analysis. Nine (9.8%) were positive. Univariate analysis showed no association between positive CT-A and any scoring system. A multivariate analysis, including age and gender, showed association between both NEWS2 and SEWS scores with positive CT-A. Conclusion In our analysis of the typical LGIB population, CT-A has shown relatively low pick up rate of active bleeding. CT-A clearly has a role in the investigation of LGIB, but selection remains challenging.

Introduction Management of malignant small bowel obstruction (mSBO) is challenging. The decision to perform an operation evaluates the perceived chance of success against a patient’s fitness for operation. The aim of this study was to characterise the mSBO patient population in a tertiary UK centre and assess the patient’s treatment pathway including use and effects of palliative surgery, total parenteral nutrition (TPN), Gastrografin and dexamethasone as well as preoperative stratification. Methods Patients were included if they had mSBO confirmed on computed tomography imaging due to a primary or metastatic neoplasm. Data were collected on pathway and management, and Cox proportional hazard methods were utilised to observe effects on survival. Results Ninety-four patients were included, with 104 inpatient episodes. Mean age was 67.4 (SD 13.7), with 57 (60.6%) females. Most (89.4%) had only one admission for mSBO. Eighty-four (89.4%) patients died over the ten-year period, 18 (17.3%) within 30 days of admission. Fifty patients (53.1%) underwent operative management: 70% bypass, 24% stoma formation and 6% open-close laparotomies. Log rank testing of survival probability analysis was significant (p = 0.00018), with 50% survival probability at 107.32 days for operative management and 47.87 days for non-operative. Discussion and Conclusion Operative management forms part of the treatment pathway for a significant proportion of patients with mSBO, offering a survival benefit, though quality of survival is not known. Case selection is good, with few open-close laparotomies. Trials of non-operative interventions such as Gastrografin and dexamethasone are not utilised fully.

The results of a parametric, numerical study of aftbody exhaust flows on a conical, airbreathing, hypersonic vehicle are presented. Three-dimensional Euler simulations were performed at Mach 9 and ...

Background: Although clinic-based palliative care (PC) services have spread in the United States, little is known about how they function, and no studies have examined clinics that predominantly se...

Objective Regional anesthesia techniques are gaining traction in cardiac surgery. The aim of this study was to compare the analgesic efficacy of erector spinae plane block catheters (ESPBC), serratus anterior plane block catheters (SAPBC), and paravertebral single-shot block (PVB) versus no block after robotic minimally invasive direct coronary artery bypass (MIDCAB). Design This was a retrospective observational study of routinely recorded data. Setting The study was performed at a single healthcare system. Participants All patients underwent robotic MIDCAB. Intervention Data were analyzed from 346 patients during a 53-month period. The clinical data warehouse was queried for all robotic MIDCAB surgeries. Variables abstracted included type of nerve block, age, sex, use of adjuncts, Society of Thoracic Surgeons predicted short length of stay (PSLOS), total opioid consumption during the 72 hours after surgery, and postoperative hospital length of stay (LOS). The primary outcome was total oral morphine milligram equivalents (MME) consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. Measurements and Main Results In a model adjusting for PSLOS, the authors did not observe an association between ESPBC and the reduction of total administered oral MME within 72 hours after surgery. There was no significant difference in MME when comparing patients who received PVB to patients with ESPBC. Older age and female sex were associated with significantly lower MME. Patients who received ESPBC had a significantly shorter hospital LOS than patients with SAPBC. Conclusions These findings suggested that postoperative pain after MIDCAB surgery might not be completely covered by ESPBC. Prospective studies are needed to further elucidate the value of this technique for robotic MIDCAB.

The serotonergic system extends throughout the central nervous system (CNS) and the gastrointestinal (GI) tract. In the CNS, serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. These processes are mediated through 5-HT binding to 5-HT receptors (5-HTRs), are classified into seven distinct groups. Deficits in the serotonergic system can result in various pathological conditions, particularly depression, schizophrenia, mood disorders, and autism. In this review, we outlined the complexity of serotonergic modulation of physiologic and pathologic processes. Moreover, we provided experimental and clinical evidence of 5-HT's involvement in neuropsychiatric disorders and discussed the molecular mechanisms that underlie these illnesses and contribute to the new therapies.

Platelet diseases and dysfunction are taught early in medical school to all future physicians. Understanding of the coagulation cascade and hemostatic mechanisms has allowed for targeted pharmacological therapies that have been significantly impactful in clinical practice. Platelets are an early participant in hemostasis physiologically and under pathophysiological states. A review of literature involving platelet disfunction. Various presentations of platelet diseases and dysfunction challenge clinicians and require a firm understanding of normal platelet function, drugs that mediate or modulate platelet effectiveness, and nonpharmacologic etiologies of platelet diseases and dysfunction with corresponding best practice treatment approaches. This review summarizes normal and abnormal states associated with platelets and treatment strategies.

Scholarship from the life-course paradigm has produced much evidence on the crime-reducing benefits of turning points such as securing a good job or developing a stable, positive relationship. Building on these insights, recent work has demonstrated the utility of incorporating health into the study of desistance; for various reasons, both mental and physical health statuses have been shown to influence the likelihood of achieving these key life-course milestones. What is less well understood, however, is how mental and physical health may interact with each other and how this model applies to certain salient subgroups in criminal justice, such as those with serious mental illnesses. Importing the mental health–crime literature, we examine both the main and synergistic effects of mental and physical health on employment focus and relationship worry among a sample of persons with serious mental illness (N = 184). Findings from logistic and ordinary least squares regression models reveal that better physical health is associated with improved employment focus and that this effect is moderated by mental health status. In addition, better physical health is associated with a decrease in worry over one’s relationships. These findings point to the value of including physical and mental health states in life-course and desistance research, studies of persons with serious mental illnesses, and intervention and policy efforts to improve lives and promote desistance.

BACKGROUND: Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels.METHODS: To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia.RESULTS: Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds.CONCLUSIONS: These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

Background The Royal College of Surgeons of England guidelines recommends laparoscopic repair for bilateral inguinal hernias, recurrent hernia after an initial open approach and Groin hernias in women. Aim This study assessed the surgical management of inguinal hernia over 6 years to see how well we adhered to national guidelines and investigated reasons for non-adherence. Methods A retrospective study from January 2013 to December 2018 of all patients undergoing inguinal hernia repair. Data collected were patient identifiers, gender, date of birth, date of admission and discharge, type of inguinal hernia, type of repair and the operating consultant. If the type of repair performed was outside of national guidance, patients’ case-notes were reviewed. Results 2593 patients were included, 93.4% male and median age of 63 (interquartile range 49-74 years). 403 patients underwent laparoscopic repair (15.5%). For unilateral primary inguinal herniae, 221 out of 2222 patients underwent laparoscopic repair (9.9%). 29 of 170 (17%) of female patients underwent laparoscopic repair. 118 out of 160 patients with bilateral hernia underwent laparoscopic repair (73.8%) - no explanation was identified for selecting open repair in 25 out of 42. Regarding recurrent hernia, 64 out of 211 patients underwent laparoscopic repair (30.3%). No explanation for selection of open approach was identified for 61 of the 147. Conclusion National guidelines recommending laparoscopic inguinal hernia repair for females, bilateral and recurrent herniae are not well followed. A likely contributing factor is the overall low rate of laparoscopic repair. Changes to practice are underway and repeat audit is planned.

Background: National data demonstrate a trend toward outpatient same-day mastectomy. The possible drivers of this change include the costs related to hospital admission and effective management of postoperative pain. We retrospectively analyzed our single-institution experience with outpatient same-day mastectomy that incorporates a multimodal pain management regimen. Methods: We retrospectively reviewed the medical records of patients who underwent same-day mastectomy at a single academic hospital. All patients received a multimodal, perioperative pain management regimen consisting of the intraoperative administration of 1,000 mg of intravenous (IV) acetaminophen and 30 mg of IV ketorolac, combined with the operating surgeon performing a 4- to 5-level, midaxillary, intercostal nerve block using liposomal bupivacaine. All patients were discharged with a prescription for acetaminophen with codeine, along with options for nonnarcotic alternatives as needed for pain. Results: We reviewed the data on 72 patients who underwent mastectomies: 11 (15.3%) bilateral and 61 (84.7%) unilateral. The average age was 57 years, and average body mass index was 30 kg/m2. The average length of stay of 4 to 6 hours was a marked reduction compared to a 23-hour observational period or an inpatient hospital stay. The average follow-up was 20.1 weeks. Five patients presented to the emergency department (ED) within the 30-day postoperative period, with 2 patients (2.8%) requiring readmission to the hospital for non–pain-related issues. The other 3 patients (4.2%) were evaluated for specific pain-related issues but did not require admission and were discharged home from the ED. Conclusion: Our data support outpatient same-day mastectomy incorporating a multimodal, perioperative pain management regimen as a safe and feasible treatment option. Potential additional benefits may include decreased oral opioid use and cost savings for the hospital.

Novel preparations allowing for the extended duration of action of local anesthetics have many clinically relevant benefits. With regard to this, the development of liposomal bupivacaine has the potential to significantly impact patient care by improving perioperative pain control. The unique liposomal bilayer that encapsulates bupivacaine allows for a sustained release of local anesthetic for up to 72 h after a single use and can significantly decrease postoperative opioid consumption. SABER-bupivacaine is another depot formulation that helps in sustained release of bupivacaine from an encapsulated bupivacaine in a biodegradable sucrose acetate isobutyrate biolayer. HTX-011 is an investigational extended-release local anesthetic formulation currently undergoing Phase 3 clinical trials. HTX-011 is composed of a bioerodible polymer with bupivacaine and low-dose meloxicam in which the polymer undergoes hydrolysis and allows for sustained release of bupivacaine and meloxicam for 3 days. The present investigation reviews pharmacologic considerations related to the formulation of liposomal bupivacaine, current FDA-approved indications for its use, and future extended-release local anesthetic formulations currently under investigation.

Purpose To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). Design Retrospective interventional case series. Participants Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. Methods Patients were divided into 3 age groups (0–6 years, 7–12 years, and 13–18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. Main Outcome Measures Complete reattachment of the retina at final follow-up. Results Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22–0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2–4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5–8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12–0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1–4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1–5.1) compared with PPV alone (51%). Conclusions Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV.

Gliomas are the most dreaded primary brain tumour because of their dismal cure rates. Ketogenic-type diets (kds) are high-fat, low-protein, and low-carbohydrate diets, the modified Atkins diet (mad) is a less-stringent version of a kd that still generates serum ketones in patients. The purpose of the present study was to retrospectively examine the feasibility of attaining ketosis and the safety of the mad in patients undergoing radiation and chemotherapy treatment for glioma. The rate of pseudoprogression (psp) after treatment was also assessed as a marker of radiation sensitization. To our knowledge, this dataset is the largest published relating to patients with glioma undergoing kd during radiation and chemotherapy. We retrospectively studied 29 patients with grades ii&ndash, iv astrocytoma following the mad during standard radiation and chemotherapy. Feasibility of attaining ketosis was assessed though levels of beta hydroxybutyrate in blood. Pre- and post-radiation magnetic resonance images were evaluated for psp by a neuroradiologist blinded to patient data. In the 29 patients who started the mad during radiation, ketosis was achieved in all 29 (100%). No serious adverse events occurred secondary to the mad. Of those 29 patients, 19 had glioblastoma multiforme. Of the latter 19 patients, 11 (58%) showed psp after mad and radiation and temozolomide therapy. A modified Atkins diet is feasible and safe for glioma patients during radiation and chemotherapy treatment. The mad and resulting ketosis could play a role as a radiation sensitizer.

BACKGROUND Colonoscopy certification in the UK is taken in two parts - provisional and full - mandating lifetime procedure counts of 200 or 300 respectively. The aim of this study was to determine the number of procedures performed by colorectal trainees by the end of training compared with gastroenterology peers and to determine factors associated with achieving the 300-procedure target for full certification. METHODS Dates of entry onto the specialist register were obtained from the GMC (General Medical Council). This list was cross-referenced with procedure counts from the JETS (JAG Endoscopy Training System) database to determine the number of colonoscopies and polypectomies performed during training. Factors associated with achieving 300 procedures were analysed by logistic regression. RESULTS Procedures numbers were obtained for 234 gastroenterology and 148 colorectal surgery trainees. Over the last 5 years, the number of colonoscopies performed during training has declined for colorectal surgery trainees but increased for gastroenterology trainees. Gastroenterology trainees are more likely to achieve provisional and full certification. For trainees completing training in 2017, 19% of colorectal surgery trainees compared with 88% of gastroenterology trainees were able to reach the threshold of 300 procedures for full certification. CONCLUSIONS Colorectal surgery trainees lag behind their gastroenterology counterparts in accruing endoscopy experience. This impacts on the ability of colorectal surgery trainees to achieve certification prior to completion of training. An urgent debate is required to decide what endoscopy training is required of a colorectal surgeon and how a robust training system can be put in place to ensure this is achieved. This article is protected by copyright. All rights reserved.

During the second wave of the COVID-19 pandemic in South Africa, a recurrent pattern of prolonged recovery after acute COVID-19 pneumonia, characterised by low oxygen saturation levels forgt;2 weeks, was observed in an intermediate-care facility in Cape Town. A case study together with a series of 12 patients is presented to illustrate this phenomenon, and two types of 'sats gap' are described, which were used by physiotherapists and doctors to monitor daily progress. We attempt to explain this prolonged recovery in terms of the possible pathophysiology, and suggest a number of learning points to guide further research.

Objective The neuroendocrine response to critical illness is dichotomous as it is adaptive during the acute phase then transitions to maladaptive as critical illness becomes prolonged in 25-30% of patients. Presently, monitoring all critically ill patients for endocrinopathies is not the standard of care. However, given the negative impact on patient prognosis, a need to identify those at risk for endocrinopathies, may exist. Thus, a screening tool to identify endocrinopathies along the somatotroph and gonadal axes in a cardiothoracic surgery population was developed. Methods A prospective observational pilot study was conducted in two cardiothoracic surgery intensive care units (ICU) within a multi-site healthcare system. Total testosterone and somatomedin C levels were obtained from 20 adult patients who remained in the ICU for greater than seven days after cardiothoracic surgery and were tolerating nutrition, had a risk of malnutrition and a mobility score of moderate to dependent assistance. Results Twenty patients were included for descriptive analysis (seven females). Thirteen patients tested low for total testosterone, with males more likely to have a testosterone-related endocrinopathy as compared to females (100% vs. 0 to 43%, p = 0.0072). A higher proportion of low somatomedin C levels was found in females than males (57% vs. 31%); however, the difference was not statistically significant (p = 0.251). Conclusions The screening tool used in this pilot study accurately predicted low total testosterone in all men and reasonably predicted low somatomedin C in a majority of women. However, the ability of the tool to predict low total testosterone in women and low somatomedin C in men is less certain. A gender-specific screening tool might be necessary to predict hormonal deficiencies.

There is a pressing need for novel immunotherapeutic targets in colorectal cancer (CRC). Cytotoxic T cell infiltration is well established as a key prognostic indicator in CRC, and it is known that these tumor infiltrating lymphocytes (TILs) target and kill tumor cells. However, the specific antigens that drive these CD8+ T cell responses have not been well characterized. Recently, phosphopeptides have emerged as strong candidates for tumor-specific antigens, as dysregulated signaling in cancer leads to increased and aberrant protein phosphorylation. Here, we identify 120 HLA-I phosphopeptides from primary CRC tumors, CRC liver metastases and CRC cell lines using mass spectrometry and assess the tumor-resident immunity against these posttranslationally modified tumor antigens. Several CRC tumor-specific phosphopeptides were presented by multiple patients’ tumors in our cohort (21% to 40%), and many have previously been identified on other malignancies (58% of HLA-A*02 CRC phosphopeptides). These shared antigens derived from mitogenic signaling pathways, including p53, Wnt and MAPK, and are therefore markers of malignancy. The identification of public tumor antigens will allow for the development of broadly applicable targeted therapeutics. Through analysis of TIL cytokine responses to these phosphopeptides, we have established that they are already playing a key role in tumor-resident immunity. Multifunctional CD8+ TILs from primary and metastatic tumors recognized the HLA-I phosphopeptides presented by their originating tumor. Furthermore, TILs taken from other CRC patients’ tumors targeted two of these phosphopeptides. In another cohort of CRC patients, the same HLA-I phosphopeptides induced higher peripheral T cell responses than they did in healthy donors, suggesting that these immune responses are specifically activated in CRC patients. Collectively, these results establish HLA-I phosphopeptides as targets of the tumor-resident immunity in CRC, and highlight their potential as candidates for future immunotherapeutic strategies.

The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region-specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L-NMMA, administered in a randomized, single-blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L-NMMA (or volume-matched saline) was infused intravenously for 5 min prior to imaging. L-NMMA reduced CBF (L-NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5-7%) in anterior and posterior cerebral circulations, due in part to the reduced cross-sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L-NMMA (L-NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7-11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. KEY POINTS: Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear. Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously. Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L-NMMA) reduced CBF by up to 11% in different brain regions. NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling.

Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of > 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

BACKGROUND: Leaders play a crucial role in implementing and sustaining changes in clinical practice, yet there is limited evidence on the strategies to engage them in team problem solving and communication. OBJECTIVE: Examine the impact of an intervention focused on facilitating leadership during daily huddles on optimizing team-based care and improving outcomes. DESIGN: Cluster-randomized trial using intention-to-treat analysis to measure the effects of the intervention (n = 13 teams) compared with routine practice (n = 16 teams). PARTICIPANTS: Twenty-nine primary care clinics affiliated with a large integrated health system in the upper Midwest; representing differing practice types and geographic settings. INTERVENTION: Full-day leadership training retreat for team leaders to facilitate of care team huddles. Biweekly coaching calls and two site visits with an assigned coach. MAIN MEASURES: Primary outcomes of team development and function were collected, pre- and post-intervention using surveys. Patient satisfaction and quality outcomes were compared pre- and post-intervention as secondary outcomes. Leadership engagement and adherence to the intervention were also assessed. KEY RESULTS: A total of 279 pre-intervention and 272 post-intervention surveys were completed. We found no impact on team development (− 0.98, 95% CI (− 3.18, 1.22)), improved team credibility (0.18, 95% CI (0.00, 0.35)), but worse psychological safety (− 0.19, 95% CI (− 0.38, 0.00)). No differences were observed in patient satisfaction; however, results were mixed among quality outcomes. Post hoc analysis within the intervention group showed higher adherence to the intervention was associated with improvement in team coordination (0.47, 95% CI (0.18, 0.76)), credibility (0.28, 95% CI (0.02, 0.53)), team learning (0.42, 95% CI (0.10, 0.74)), and knowledge creation (0.74, 95% CI (0.35, 1.13)) compared to teams that were less engaged. CONCLUSIONS: Results of this evaluation showed that leadership training and facilitation were not associated with better team functioning. Additional components to the intervention tested may be necessary to enhance team functioning. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03062670. Registration Date: February 23, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03062670 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06487-6.

(1) Background: Internal medicine (IM) resident physicians need to be trained to care for older adults and transition them safely across care settings. Objective: The study purpose was to evaluate the efficacy of a curriculum in geriatrics assessment and communication skills for transitions of care (TOCs) to IM resident physicians. (2) Methods: IM residents rotated for 4 weeks on the geriatrics consult service at a large public teaching hospital, where they received didactic lectures and clinical experience in consultation and transitional care. The curriculum was designed to meet consensus guidelines for minimum geriatrics competencies expected of IM residents. Previously validated and published assessment tools were used for geriatrics knowledge and attitudes. Locally developed tools were used to directly observe and rate communication skills, and self-assess geriatrics assessment and health literacy skills. The curriculum was evaluated using a quasi-experimental, nonrandomized, single-group pre- and post-test observational design. Data on 31 subjects were collected over 18 months and analyzed using mixed-effects models. (3) Results: Average knowledge scores improved from 65% to 74% (&Delta, 9%, 95% CI 4&ndash, 13%, p &lt, 0.001). Communication skills improved by an average of 1.15 points (95% CI 0.66&ndash, 1.64, p &lt, 0.001) on a 9-point scale. Attitudes did not change significantly. Self-rated confidence in geriatrics assessment and health literacy skills improved modestly. (4) Conclusions: The curriculum is effective in teaching basic geriatrics knowledge and communication skills, and increasing self-confidence in geriatrics assessment skills. In settings where an inpatient geriatrics consult service is feasible, the curriculum may be a model for combining geriatrics and TOC training.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Psychiatric genomics is a rapidly growing field that holds much promise for improving risk prediction, prevention, diagnosis, treatment selection, and understanding of the pathogenesis of patients' symptoms. The field of psychiatry (i.e., professional organizations, mental health clinicians, educational institutions), however, needs to address numerous challenges to promote the responsible translation of genomic technologies and knowledge into psychiatric practice. The goal of this article is to review how clinicians currently encounter and use genomics in the clinic, to summarize the existing literature on how clinicians feel about the use of genomics in psychiatry, and to analyze foreseeable ethical and legal challenges for the responsible integration of genomics into psychiatric care at the structural and clinic levels. Structural challenges are defined as aspects of the larger system of psychiatric practice that constitute potential barriers to the responsible integration of genomics for the purposes of psychiatric care and prevention. These structural challenges exist at a level where professional groups can intervene to set standards and regulate the practice of psychiatry and genomics. Clinic-level challenges are day-to-day issues clinicians face when managing genomic tests in the clinic. We discuss the need for action to mitigate these challenges and maximize the clinical and social utility of psychiatric genomics, including the following: expanding genomics training among mental health clinicians; establishing practice guidelines that consider potential clinical, psychological, and social implications of psychiatric genomics; promoting an integrated care model for managing genomics in psychiatry; emphasizing patient engagement and informed consent when managing genomic testing in psychiatric care.

Objective The optimal regional technique for minimally invasive direct coronary artery bypass (MIDCAB) has yet to be determined. The aim of this study was to compare the efficacy of ultrasound-guided serratus anterior plane block (SAPB) with paravertebral block (PVB) and no block for controlling acute thoracotomy pain after robotic-assisted coronary artery bypass grafting (CABG). Design This is a retrospective study. Multiple variable regression analyses were performed. Setting The study was performed as a single institution. Participants All patients underwent robotic-assisted CABG. Intervention Data were analyzed from 197 patients during a 27-month period. Charts were abstracted manually to ascertain type of nerve block, age, gender, use of home opioids, use of adjuncts for opioid reduction, Society of Thoracic Surgeons predicted long length of stay (LOS), total opioid consumption during the 72 hours after surgery, and postoperative LOS. The authors’ primary outcome was total morphine equivalents consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. Measurements and Main Results Patients who received SAPB did not have significantly different opioid consumption than patients who had no block (p = 0.15), but it was increased significantly compared to patients administered PVB (PVB v SAPB catheter, p = 0.049; PVB v SAPB single shot, p = 0.049). There were no significant differences between groups in terms of postoperative LOS. Conclusion These findings suggest SAPB might not cover adequately the incisional and tube pain associated with MIDCAB. If validated by prospective studies, these findings suggest that SAPB should be considered only for patients who are not candidates for PVB.

Background Team-based care has been identified as a key component in transforming primary care. An important factor in implementing team-based care is the requirement for teams to have daily huddles. During huddles, the care team, comprising physicians, nurses, and administrative staff, come together to discuss their daily schedules, track problems, and develop countermeasures to fix these problems. However, the impact of these huddles on staff burnout over time and patient outcomes are not clear. Further, there are challenges to implementing huddles in fast-paced primary care clinics. We will test whether the impact of a behavioral intervention of leadership training and problem-solving during the daily huddling process will result in higher consistent huddling in the intervention arm and result in higher team morale, reduced burnout, and improved patient outcomes. Methods/design We will conduct a care-team-level cluster randomized trial within primary care practices in two Midwestern states. The intervention will comprise a 1-day training retreat for leaders of primary care teams, biweekly sessions between huddle optimization coaches and members of the primary care teams, as well as coaching site visits at 30 and 100 days post intervention. This behavioral intervention will be compared to standard care, in which care teams have huddles without any support or training. Surveys of primary care team members will be administered at baseline (prior to training), 100 days (for the intervention arm only), and 180 days to assess team dynamics. The primary outcome of this trial will be team morale. Secondary outcomes will assess the impact of this intervention on clinician burnout, patient satisfaction, and quality of care. Discussion This trial will provide evidence on the impact of a behavioral intervention to implement huddles as a key component of team-based care models. Knowledge gained from this trial will be critical to broader deployment and successful implementation of team-based care models. Trial registration Clinicaltrials.gov , NCT03062670 . Registered on 23 February 2017.

AIM Previous studies have raised concerns that the use of anti-tumour necrosis factor (anti-TNF) therapy in patients with ulcerative colitis (UC) undergoing surgery may increase the risk of postoperative complications. We have taken a population-based approach to investigate whether there is an association between anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. METHOD Hospital Episode Statistics (HES) data and procedural coding were used to identify all patients in England between April 2006 and March 2015 undergoing subtotal colectomy for UC. Patients were grouped into those who received anti-TNF therapy within 12 or 4 weeks of surgery and those who did not. The incidence of postoperative complications was evaluated by HES coding and compared between groups. RESULTS In all, 6225 UC patients underwent subtotal colectomy. 753 patients received anti-TNF therapy within 12 weeks prior to surgery (418 within 4 weeks). There was no difference in postoperative complications between groups although groups were not comparable for age and comorbidities. Logistic regression with complications as the outcome variable did not show any significant association between anti-TNF therapy and complications. Colectomy performed during an unplanned admission (vs planned admission) and smoking were associated with complications. CONCLUSION This large population-based study does not demonstrate any association between preoperative anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. The only variables associated with complications were colectomy performed during an unplanned admission and smoking.

BACKGROUND Diverticular disease accounts for significant morbidity and mortality and may take the form of recurrent episodes of acute diverticulitis. The role of elective surgery is not clearly defined. OBJECTIVE This study aimed to define the rate of hospital admission for recurrent acute diverticulitis and risk factors associated with recurrence and surgery. DESIGN This is a retrospective population-based cohort study. SETTINGS National Health Service hospital admissions for acute diverticulitis in England between April 2006 and March 2011 were reviewed. PATIENTS Hospital Episode Statistics data identified adult patients with the first episode of acute diverticulitis (index admission), and then identified recurrent admissions and elective or emergency surgery for acute diverticulitis during a minimum follow-up period of 4 years. Exclusion criteria included previous diagnoses of acute diverticulitis, colorectal cancer, or GI bleeding, and prior colectomy or surgery or death during the index admission. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES The primary outcomes measured were recurrent admissions for acute diverticulitis and patients requiring either elective or emergency surgery during the study period. RESULTS Some 65,162 patients were identified with the first episode of acute diverticulitis. The rate of hospital admission for recurrent acute diverticulitis was 11.2%. A logistic regression model examined factors associated with recurrent acute diverticulitis and surgery: patient age, female sex, smoking, obesity, comorbidity score >20, dyslipidemia, and complicated acute diverticulitis increased the risk of recurrent acute diverticulitis. There was an inverse relationship between patient age and recurrence. Similar factors were associated with elective and emergency surgery. LIMITATIONS The cases of acute diverticulitis required inpatient management and the use of Hospital Episode Statistics, relying on the accuracy of diagnostic coding. CONCLUSIONS This is the largest study assessing the rates of hospital admission for recurrent acute diverticulitis. Knowledge of the rate and risk factors for recurrent acute diverticulitis is required to aid discussion and decision making with patients regarding the need and timing of elective surgery. Some factors associated with recurrence are modifiable; therefore, weight reduction and smoking cessation can be championed. See Video Abstract at http://links.lww.com/DCR/A449.

Organizational performance is often dependent on the timing of critical processes and the simultaneous use of both technology and routines. Existing publications emphasize the importance of time sensitivity but also reflect divergent, untested perspectives. Prior works do not clearly explain or examine how different mechanisms are associated with achieving time-sensitive versus general (or non-time-sensitive) performance. We build on concepts from organizational mindfulness and organizational routines to address these gaps. Specifically, this paper examines how the mindful use of information technologies and adherence to specified routines are associated with both time-sensitive and general organizational performance. We employ split-group structural equation modeling based on high and low levels of information technology adoption to account for potential technology contingencies in performance. We use time-sequenced data from 262 U.S. hospitals to analyze two categories of clinical care quality: time-sensitive care and general care. The results indicate that mindful use of technologies is associated with both time-sensitive and general performance in contexts with high technology adoption but not in those with low adoption. In contrast, adherence to specified routines is associated with time-sensitive performance in contexts with low technology adoption but not in those with high adoption. The results also clarify that high levels of technology adoption and mindful use may at times assume the place of specified routines in their association with time-sensitive performance. Finally, we find evidence that continuous improvement may bridge adherence to specified routines and mindful use of technologies.

Background/aims Traditionally, patients with acute diverticulitis undergo follow-up endoscopy to exclude colorectal cancer (CRC). However, its usefulness has been debated in this era of high-resolution computed tomography (CT) diagnosis. We assessed the frequency and outcome of endoscopic follow-up for patients with CT-proven acute diverticulitis, according to the confidence in the CT diagnosis. Methods Records of patients with CT-proven acute diverticulitis between October 2007 and March 2014 at Sandwell & West Birmingham Hospitals NHS Trust were retrieved. The National Cancer Registry confirmed the cases of CRC. Endoscopy quality indicators were compared between these patients and other patients undergoing the same endoscopic examination over the same period. Results We identified 235 patients with CT-proven acute diverticulitis, of which, 187 were managed conservatively. The CT report was confident of the diagnosis of acute diverticulitis in 75% cases. Five of the 235 patients were subsequently diagnosed with CRC (2.1%). Three cases of CRC were detected in the 187 patients managed conservatively (1.6%). Forty-eight percent of the conservatively managed patients underwent follow-up endoscopy; one case of CRC was identified. Endoscopies were often incomplete and caused more discomfort for patients with diverticulitis compared with controls. Conclusions CRC was diagnosed in patients with CT-proven diverticulitis at a higher rate than in screened asymptomatic populations, necessitating follow-up. CT reports contained statements regarding diagnostic uncertainty in 25% cases, associated with an increased risk of CRC. Follow-up endoscopy in patients with CT-proven diverticulitis is associated with increased discomfort and high rates of incompletion. The use of other follow-up modalities should be considered.

BACKGROUND The treatment of spinal muscular atrophy (SMA) with nusinersen requires intrathecal medication administration, which can be challenging in individuals with complicated spines. This retrospective case series reviews the nusinersen treatment experience at one academic medical center with children and adults with SMA and complicated spines. METHODS Twenty medical records of individuals receiving nusinersen were reviewed and administration methods summarized and assessed. RESULTS Ten children and 10 adults were treated, and 55% had complicated spines. In total, 163 treatments were given, 91 in those with complicated spines. In the complicated spines, 74% of treatments were done by means of fluoroscopic lumbar puncture, 22% by means of intrathecal Ommaya reservoir, 3% by means of palpation, and

Introduction and objectives Although advanced COPD is associated with poor survival, individual trajectories are difficult to predict and clinician ability to recognise those in the last year of life is unknown. Factors which are prognostic for mortality have been identified across the spectrum of COPD severity. Whether they retain prognostication in advanced disease is also unknown. We investigated clinician prognostication and clinically measurable prognostic factors for mortality in patients with advanced COPD. Methods Patients were recruited from an advanced COPD service between October 2013 and July 2018 forming a prospective observational cohort. Measures collected at baseline included spirometry, MRC dyspnoea grade, body mass index (BMI), four metre gait speed (4MGS), exacerbation history, home-oxygen use and presence of comorbidities. Clinicians’ prediction of one year mortality was recorded in response to the ‘Surprise Question’: ‘Would I be surprised if this patient died within the next 12 months?’. Receiver operating characteristic (ROC) analysis was performed to determine the accuracy of clinician assessment of prognosis. Mortality data were censored at February 2019. Survival analysis was performed using multivariate Cox regression. Results 398 were patients recruited, 59% male, 24% current smokers, mean±SD age 66±9 yr, FEV1% predicted 35±13%, BMI 26±7 kg/m2, 88% MRC dyspnoea scale grade ≥4, 29% used home oxygen, 91% had a COPD exacerbation in the past year, and 88% had co-morbidities. Average follow-up time was 888 days, 145 deaths (36%) occurred and one-year mortality rate was 12%. The positive and negative predicted values for clinicians’ prediction of one-year mortality were 24% and 93%, with an area under ROC of 0.65. Adjusted time to event analysis for patients with complete baseline data (n=277) showed older age, lower BMI and slower 4MGS were independently associated with increased risk of mortality (Table 1). Conclusions In patients with advanced COPD, clinicians do not accurately identify those within the last year of life. Alongside age and BMI, 4MGS is an independent predictor of mortality in advanced COPD. A prognostic scoring system including these indices has the potential to assist clinicians identify patients in the last year of life supporting proactive development of advance care plans.

BACKGROUND The learning curve in paediatric oesophagogastroduodenoscopy (OGD) is unknown. Using ≥95% D2 (second part of the duodenum) intubation rates as a marker of technical competency, we conducted learning curve analyses to identify when trainees achieve competency in paediatric OGD. Factors associated with competency were also evaluated. METHODS This nationwide study analysed data from paediatric OGD procedures prospectively entered into the UK endoscopy training e-portfolio between 2014 and 2018. Moving average and learning curve cumulative summation analyses were performed to determine procedural numbers required to achieve ≥95% D2 intubation rates. Factors associated with D2 intubation were assessed using a multivariable binary logistic regression approach. RESULTS A total of 8929 procedures performed by 61 trainees were identified. These 61 trainees had recorded a mean of 124.6 procedures (range 22-571, interquartile range 165). By moving average analysis, 95% D2 intubation was achieved after 79 procedures. By learning curve cumulative summation analysis, 81.6% of trainees were competent after 100 procedures. Multivariable factors associated with unassisted procedural completion included: lifetime procedure count (P

ObjectivesEthnic/racial minority groups are less likely to discuss issues involving end-of-life treatment preferences and utilize palliative care or hospice services. Some barriers may be differences in language, religion, lower levels of health literacy, or less access to healthcare services and information. The purpose of this article is to conduct a systematic review on interventional studies that investigated methods to overcome the barriers faced by ethnic/racial minorities when accessing end-of-life services, including completing advanced directives, accepting palliative care, and enrolling in hospice.MethodsLiterature searches using four standard scientific search engines were conducted to retrieve articles detailing original research in an interventional trial design. All studies were conducted in an outpatient setting, including primary care visits, home visits, and dialysis centers. Target populations were those identified from ethnic or racial minorities.ResultsNine articles were selected to be included in the final review. All were full-text English language articles, with target populations including African Americans, Hispanic or Latinos, and Asian or Pacific Islanders. Measured outcomes involved level of comfort in discussing and knowledge of palliative care services, desire for aggressive care at the end-of-life, completion of advance directives, and rate of enrollment in hospice.Significance of ResultsThree main avenues of interventions included methods to enhance patient education, increase access to healthcare, or improve communication to establish better rapport with target population. Studies indicate that traditional delivery of healthcare services may be insufficient to recruit patients from ethnic/racial minorities, and outcomes can be improved by implementing tailored interventions to overcome barriers.

Diabetic ketoacidosis (DKA) is a potentially fatal endocrine emergency resulting from uncontrolled diabetes mellitus (DM). The development of DKA has been linked to a number of precipitating factors such as infectious process, ischemia, medications, and other medical-surgical illnesses. These factors have been found to aggravate or unmask pre-existing glucose dysregulation secondary to absolute or relative insulin deficiency and increased levels of counter-regulatory hormones. We describe the case of a 61-year-old male with a history of insulin dependent DM who develops DKA postoperatively after a three-vessel coronary artery bypass surgery and mitral valve repair while in the intensive care unit (ICU). The patient’s postoperative course was complicated by presumed pneumonia and hyperactive delirium. On postoperative day (POD) five, the patient’s insulin infusion was held due to non-symptomatic hypoglycemia. Eleven hours later, the insulin infusion was resumed to treat DKA after laboratory findings revealed hyperglycemia, an elevated β-hydroxybutyrate, and anion gap metabolic acidosis. Multiple contributing factors for the development of DKA are suspected and discussed. It is paramount that clinicians are knowledgeable of the multiple factors that can contribute to the development of DKA in the ICU.

To identify hospital staffing models associated with failure to rescue (FTR) rates at low- and high-performing hospitals.FTR is an important quality measure in surgical safety and is a metric that hospitals are seeking to improve. Specific unit-level determinants of FTR, however, remain unknown.Retrospective, observational study using data from the Michigan Quality Surgical Collaborative, which is a prospectively collected and clinically audited database in the state of Michigan. We identified 44,567 patients undergoing major general or vascular surgery from 2008 to 2012. Our main outcome measures were mortality, complications, and FTR rates.Hospital rates of FTR across low, middle, and high tertiles were 8.9%, 16.5%, and 19.9%, respectively (P0.001). Low FTR hospitals tended to have a closed intensive care unit staffing model (56% vs 20%, P0.001) and a higher proportion of board-certified intensivists (88% vs 60%, P0.001) when compared to high FTR hospitals. There was also significantly more staffing of low FTR hospitals by hospitalists (85% vs 20%, P0.001) and residents (62% vs 40%, P0.01). Low FTR hospitals were noted to have more overnight coverage (75% vs 45%, P0.001) as well as a dedicated rapid response team (90% vs 60%, P0.001).Low FTR hospitals had significantly more staffing resources than high FTR hospitals. Although hiring additional staff may be beneficial, there remain significant financial limitations for many hospitals to implement robust staffing models. Thus, our ongoing work seeks to improve rescue and implement effective staffing strategies within these constraints.

Fluoroquinolones are commonly prescribed antimicrobials that have been implicated in alterations of glucose metabolism. We report a case of refractory fluoroquinolone-induced hypoglycemia in a patient with type-2 diabetes mellitus on glipizide that was successfully treated with octreotide. A patient was admitted with hypoglycemia after having been initiated on levofloxacin therapy. Despite treating the hypoglycemia supportively with multiple boluses of 25 g of dextrose, a continuous dextrose infusion, and glucagon, the patient experienced repeated episodes of rebound hypoglycemia. The persistent hypoglycemia was eventually reversed with the administration of subcutaneous octreotide. Clinicians should be cognizant of this adverse effect of fluoroquinolones, as well as predisposing risk factors, and consider octreotide as an adjunctive therapy for refractory hypoglycemia cases.

Gas hydrates are crystalline solids comprised of a three-dimensional network of water cages that can trap small hydrocarbon molecules at high pressure and low temperature. Formation of gas hydrates can lead to blockages in subsea oil and gas flowlines, where these conditions are readily achieved. As gas reserves mature over time, new CO2-rich reservoirs can be prolific hydrocarbon producers for markets willing to bear the additional production costs. However, there is a lack of understanding about the formation behavior and growth morphology of CO2-rich hydrates. In this work, hydrate growth rate and resistance-to-flow (torque) data for a ternary CO2-rich gas mixture were measured in a high-pressure sapphire autoclave apparatus and were compared with baseline data for a pure methane system. Images of hydrate growth and eventual plug formation were captured for methane hydrate and ternary gas systems, where early hydrate growth in the latter was dominated by an opaque film nucleating at the gas-water-wall interface and growing into both gas and water phases with time. Only 7 vol% methane hydrate was required to increase the motor torque above its baseline value, while at least 20 vol% hydrate was required when formed from the CO2-rich ternary gas. These new observations provide insight into the effect of guest species solubility on hydrate growth and resistance-to-flow in the resultant slurries, which are key parameters when assessing the risk of hydrate blockage in oil and gas pipelines.

This study aimed to analyse variations in intravenous fluid therapy and electrolyte management with variable rate intravenous insulin infusions (VRIIIs); and to quantify serum electrolyte changes pre- versus post-VRIII and variations therein depending on supplemented fluid electrolyte compositions. A retrospective study was undertaken involving 174 VRIIIs prescribed over a 10-week period at a tertiary teaching hospital. Each VRIII had their associated fluid prescription and serum electrolytes analysed. The results showed that 5% dextrose (46%) and 0.9% NaCl (34%) were the most commonly prescribed fluids; 64% of fluids did not have the recommended potassium supplementation. Administration of a VRIII resulted in a significant drop in serum potassium levels (p < 0.0001) for those who did not receive supplementation. There was no drop in serum potassium for those patients who did receive supplemental potassium. Eleven patients (6.4%) developed new-onset hypokalaemia (K ≤3.5 mmol/L) after implementation of a VRIII. Our study supports the hypothesis that VRIIIs cause hypokalaemia and that this can be averted by supplemental potassium, thus preventing potentially avoidable hypokalaemic complications. A large variation exists in prescribing fluids with VRIIIs. Introduction of the national surgical and medical VRIII guidelines, together with improved availability to recommended fluids, and a quality improvement project, are our next steps to improve patient outcomes. Copyright © 2016 John Wiley & Sons.

The Atacama Cosmology Telescope Polarimeter (ACTPol) is a polarization sensitive receiver for the 6-m Atacama Cosmology Telescope (ACT) and measures the small angular scale polarization anisotropies in the cosmic microwave background (CMB). The full focal plane is composed of three detector arrays, containing over 3000 transition edge sensors (TES detectors) in total. The first two detector arrays, observing at 146 GHz, were deployed in 2013 and 2014, respectively. The third and final array is composed of multichroic pixels sensitive to both 90 and 146 GHz and saw first light in February 2015. Fabricated at NIST, this dichroic array consists of 255 pixels, with a total of 1020 polarization sensitive bolometers and is coupled to the telescope with a monolithic array of broad-band silicon feedhorns. The detectors are read out using time-division SQUID multiplexing and cooled by a dilution refrigerator at 110 mK. We present an overview of the assembly and characterization of this multichroic array in the lab, and the initial detector performance in Chile. The detector array has a TES detector electrical yield of 85 %, a total array sensitivity of less than 10 $$\upmu $$ K $$\sqrt{\text {s}}$$ , and detector time constants and saturation powers suitable for ACT CMB observations.

The aim of this study was to determine the number of OGDs (oesophago-gastro-duodenoscopies) trainees need to perform to acquire competency in terms of successful unassisted completion to the second part of the duodenum 95% of the time.OGD data were retrieved from the trainee e-portfolio developed by the Joint Advisory Group on GI Endoscopy (JAG) in the UK. All trainees were included unless they were known to have a baseline experience of20 procedures or had submitted data for20 procedures. The primary outcome measure was OGD completion, defined as passage of the endoscope to the second part of the duodenum without physical assistance. The number of OGDs required to achieve a 95% completion rate was calculated by the moving average method and learning curve cumulative summation (LC-Cusum) analysis. To determine which factors were independently associated with OGD completion, a mixed effects logistic regression model was constructed with OGD completion as the outcome variable.Data were analysed for 1255 trainees over 288 centres, representing 243 555 OGDs. By moving average method, trainees attained a 95% completion rate at 187 procedures. By LC-Cusum analysis, after 200 procedures,90% trainees had attained a 95% completion rate. Total number of OGDs performed, trainee age and experience in lower GI endoscopy were factors independently associated with OGD completion.There are limited published data on the OGD learning curve. This is the largest study to date analysing the learning curve for competency acquisition. The JAG competency requirement for 200 procedures appears appropriate.

// Henry J.M. Ferguson 1, 2, * , Joseph W. Wragg 1, * , Stephen Ward 2 , Victoria L. Heath 1 , Tariq Ismail 2 , Roy Bicknell 1 1 Molecular Angiogenesis Group, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK 2 Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, B15 2TH, UK * These authors have contributed equally to this work Correspondence to: Henry J.M. Ferguson, e-mail: fergusonh@doctors.org.uk Keywords: colorectal cancer, GRIN2D, tumour endothelial marker, vaccination, active immunotherapy Received: November 11, 2015 Accepted: January 31, 2016 Published: March 01, 2016 ABSTRACT Current vascular-targeted therapies in colorectal cancer (CRC) have shown limited benefit. The lack of novel, specific treatment in CRC has been hampered by a dearth of specific endothelial markers. Microarray comparison of endothelial gene expression in patient-matched CRC and normal colon identified a panel of putative colorectal tumour endothelial markers. Of these the glutamate dependent NMDA receptor GRIN2D emerged as the most interesting target. GRIN2D expression was shown to be specific to colorectal cancer vessels by RTqPCR and IHC analysis. Its expression was additionally shown be predictive of improved survival in CRC. Targeted knockdown studies in vitro demonstrated a role for GRIN2D in endothelial function and angiogenesis. This effect was also shown in vivo as vaccination against the extracellular region of GRIN2D resulted in reduced vascularisation in the subcutaneous sponge angiogenesis assay. The utility of immunologically targeting GRIN2D in CRC was demonstrated by the vaccination approach inhibiting murine CRC tumour growth and vascularisation. GRIN2D represents a promising target for the future treatment of CRC.

We investigate service delivery in one specific type of professional service firms (PSF), namely hospitals. A distinctive operational feature of this setting is that the delivery of health care services requires continuous collaboration between two professional workforces: physicians and nurses. We conducted a multiple-case study at five acute care U.S. hospitals, which involved 49 semi-structured interviews, to uncover the organizational mechanisms that facilitate effective collaboration between physicians and nurses. Our analyses suggest that they experience distinct challenges that prevented collaboration during health care delivery. Specifically, physicians typically favored evidence-based standards of care which can sometimes undermine patient interactions. We refer to this preference as a disease-focus challenge. We also found that nurses were often hesitant to speak-up during their interactions with the physicians, which constitute a hierarchical challenge. Commonly prescribed mechanisms, such as multi-disciplinary rounding, were not effective in overcoming these challenges. Our analyses revealed new forms of collaboration between different levels of the physician and nursing entities, which we denote as “nursing-led cross-level collaboration” and “physician-led cross-level collaboration”. Our study suggests that nursing-led cross-level collaboration helped mitigate the disease-focus challenge experienced by physicians while physician-led cross-level collaboration helped mitigate the hierarchical challenge experienced by nurses. It also offers preliminary insights on how PSF in general can develop and sustain such collaboration. Taken together, our findings offer new insights on the micro-foundations of work performed by PSF.

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to 4 distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca(2+)(i)), and ERK and p38(MAPK) phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p=0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC(50)) at lower concentrations of extracellular calcium (Ca(2+)(o)) compared to wild type (WT) CaR; NPSP795 exposure increased the EC(50) for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype, or the response to calcilytics, suggesting that other parameters impact the response to the drug.